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Gestational Intermittent Hypoxia Reduces Basal Levels of Interleukin‐1 alpha Gene Expression in Neonatal Brainstem Microglia: Implications for Respiratory Control
Author(s) -
Knutson Andrew Owen,
Ewald Andrea,
Kiernan Elizabeth,
Baker Tracy,
Watters Jyoti
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.730.6
Subject(s) - microglia , brainstem , hypoxia (environmental) , endocrinology , fetus , intermittent hypoxia , medicine , biology , offspring , respiratory system , cytokine , inflammation , pregnancy , obstructive sleep apnea , chemistry , genetics , organic chemistry , oxygen
The in utero environment strongly impacts the developing fetus, and perturbations during this critical developmental window can have long lasting, negative consequences on offspring physiology. Intermittent hypoxia, a hallmark of obstructive sleep apnea, causes profound inflammation, is common during the third trimester of pregnancy, and is rising in parallel with the obesity epidemic. Although maternal immune activation is well‐known to influence fetal brain development and microglial immune activities, the consequences of gestational intermittent hypoxia (GIH) on microglia in CNS regions essential for respiratory neural control have not been studied. Given the important role of microglia in brain development during the first 2 postnatal weeks of life, and the importance of the critical period in postnatal respiratory development, we evaluated inflammatory gene expression in brainstem microglia in 14 day old (P14) rat pups whose dams were exposed to intermittent hypoxia (2 minutes alternating between 21% O‐ 2 /10.5% O‐ 2 ) or normoxia (alternating between 21% O 2 /21% O 2 ; GNX) for 8hrs/day during gestational days 10–21. Microglia were immunomagnetically isolated from the brainstems of GNX and GIH P14 pups, and inflammatory gene expression was analyzed by qRT‐PCR. While there were sex‐dependent differences in the basal expression of several key inflammatory cytokine genes in brainstem microglia, we focus here on interleukin‐1 alpha (IL‐1α). The expression of IL‐1α was 3.5‐fold higher in GNX female microglia than in male (p=0.014; N=5 each), indicating a strong sexual dimorphism in the expression of this cytokine in normal brainstem microglia. Very interestingly however, IL‐1α mRNA levels were significantly reduced by GIH only in female microglia (p=0.03; N=5 each), although they approximated those in GNX male microglia. IL‐1α is a unique cytokine in that it is an alarmin‐ a molecule that is released early after insult that signals tissue damage and activates the immune system. It has not been specifically studied in the respiratory neural control system to our knowledge, but the downregulation of IL‐1α by GIH in female brainstem microglia may reflect a compensatory response that is absent in males to combat the inflammatory uterine environment caused by maternal intermittent hypoxia. Studies are currently underway to further investigate the role of IL‐1α in respiratory neural control. Support or Funding Information Supported by NS085226, HL105511, and Wisconsin Alumni Research Foundation UW2020 grant This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .